Device for closing a sample receptacle with a spherical closure element

ABSTRACT

The invention relates to a device for closing a sample container with a spherical closing element, wherein the device has a storage container for a plurality of spherical closing elements, ejecting means for ejecting one of the closing elements through a discharge opening in a housing of the device, and means for limiting the forces exerted by the ejecting means on the closing element.

The invention relates to a device for closing a sample container with a spherical closing element, and also a system comprising such a device and a corresponding sample container.

Sample containers are used in particular within the scope of biotechnological methods in order to process a biological sample or a biological material, such as a sample containing nucleic acids. These sample containers can be used for example to duplicate nucleic acids in vitro within the scope of amplification reactions, such as a polymerase chain reaction (PCR). Here, the sample containers are used to receive the sample comprising the nucleic acids.

A large number of different sample containers that are routinely used as disposable products within the scope of appropriate biotechnological methods, such as PCR, are known from the prior art. Here, the sample containers are firstly filled with the sample, then closed in an airtight manner, and lastly supplied to the PCR process. Here, high demands are placed on the closure of the sample containers. On the one hand, the sample containers have to be reliably tightly sealed so as not to compromise the result of the PCR process by the entry and exit of sample material or by an undesired pressure change. On the other hand, a large number of samples and therefore of sample containers are routinely used within the scope of a PCR process and have to be filled and closed. This should therefore be performed in an automated manner where possible. Furthermore, it must be possible to produce the sample containers cost-effectively, in particular because they are required in high number and are used as disposable products.

A sample container is known from EP 0 449 425 A2, wherein one end of a cylindrical housing, which forms a sample space, is provided with a circular opening that extends in a channel-shaped manner into the sample space. The opening channel tapers shortly before the transition into the sample space and thus forms a seal seat for a spherical closing element. Once the closing element has been fitted onto the seal seat, it is fixed by means of a closing plug.

As a three-part system, the sample container known from EP 0 449 425 A2 is not only relatively complex and therefore expensive, but can also only be closed in an automated manner with relatively high effort.

Proceeding from this prior art, the object of the invention was to specify a system comprising a sample container and a device, said system ensuring reliable automated closure of the sample container.

This object is achieved by a device according to independent claim 1 and by a system comprising such a device and a sample container according to independent claim 12. Independent claim 16 relates to a storage container which is to be used in conjunction with the device according to the invention according to claim 1. Advantageous developments of the device according to the invention, of the system according to the invention and of the storage container according to the invention are disclosed in the respective dependent claims and will emerge from the following description of the invention.

The system according to the invention comprises a sample container which has a housing which forms a sample space for receiving a sample and has at least one spherical opening, which extends in a channel-shaped manner into the sample space. The sample container can be closed by means of a spherical closing element, the diameter of the closing element exceeding the diameter of the opening channel in at least one (closing) portion only to an extent that one of the closing elements can be fixed in a force-locked manner by its largest circumference in the closing portion.

The force-locked fixing of the closing element by contact between a region comprising the largest circumference of the spherical closing element and the wall of the opening channel is important in order to achieve a secure fixing. The resultant forces with this type of force-locked fixing specifically comprise no, or only a relatively small (and therefore negligible), force components in the longitudinal axial direction of the opening channel, but these are directed (largely) radially in the direction of the centre of the spherical closing element. Sufficient fixing and, at the same time, a good sealing effect can thus be produced with only a relatively small (preferably elastic) deformation of the closing element and of the wall of the opening channel. A small deformation then also requires only relatively small forces in order to introduce the closing element into the opening channel. This can not only simplify the automation of the closing of the sample container but also enable manual closing of the sample container. In addition, the requirements of the materials used for the closing element and the housing are reduced, whereby the production costs for the sample container can be kept low.

In the case of the sample container of the system according to the invention, the spherical closing element not only effects sealing in conjunction with the housing of the sample container, but it is reliably fixed without additional retaining means, for example a closing plug, as is known from the sample container in EP 0 449 425 A2. Such a sample container can accordingly be closed easily in an automated manner in that the closing element is merely driven in a suitable manner into the opening channel of the housing.

In order to close such a sample container, the system according to the invention has a device which comprises a storage container for a plurality of spherical closing elements and also ejecting means for ejecting one of the closing elements through a discharge opening in a housing of the device. Thus, in order to close the sample container, one of the spherical closing elements is driven by means of the ejecting means of the device into the opening channel of the housing of the sample container and is fixed in a force-locked manner there.

Provided in the device according to the invention are means which limit the forces exerted by the ejecting means (preferably ram) on the closing element. These can serve to limit the loading of the closing element or of the housing, loaded thereby, of a sample container. In particular, the advancement control of the ram can be subjected to less stringent requirements as a result, since an excessive stroke of the ram can be compensated by the force limitation and thus excessive driving of the closing element into the opening channel of the sample container can be avoided.

The means for force limitation can be formed preferably as (at least one) spring which is arranged for example between the ram and the drive means which effect the periodic movement of the ram. An excessive stroke of the ram can then be compensated by an elastic deformation of the spring. Of course, it is also possible to arrange the spring at any desired point in the force flow between the drive means and the support of the sample container. For example, the sample container can be spring-mounted in a receptacle or the receptacle is spring-mounted in a corresponding manner. The spring is preferably integrated into the device in a preloaded manner in order to allow it to respond only when a defined force is exceeded.

On the other hand, it is of course also possible to control the introduction of force by the ejecting means onto the closing element by electronic control of the ejecting movement.

In a preferred embodiment of the device for closing, the ejecting means may comprise a ram. This makes it possible to drive one of the closing elements into the opening channel of the sample container in a structurally simple manner.

Since the device according to the invention for closing a multiplicity of sample containers is preferably used with a short cycle, the ram may preferably be driven by means of suitable drive means in a periodic (to-and-fro) movement. The device should then be used in combination with an apparatus which, in a cycle corresponding to the periodic movement of the ram, either supplies the individual sample containers to be closed to the device according to the invention or allows the device according to the invention to discharge the individual sample containers in succession.

The drive means for the periodic movement of the ram may preferably have a rotary drive which is connected to the ram via a gear mechanism in order to convert the rotary movement of the rotary drive into the periodic translation movement of the ram.

In a preferred embodiment, the rotary drive may for this purpose have a drive disc on which a bolt is decentrally arranged, which is guided in a slot of the ram or of a guide element connected to the ram, wherein the alignment of the slot is not parallel to (also not coaxial with) the direction of movement. As a result, the rotary movement of the drive disc can be converted into a periodic translation movement of the ram in a structurally simple manner. In order to drive the ram in a periodic translation movement, use can be made for this purpose of rotary drives (in particular electric rotational motors) which are available cost-effectively on the market. Of course, it is also possible to provide any other desired connection between the drive disc and the ram or the guide element of the ram.

The drive means can of course also be formed in any other desired manner, for example by way of a toggle lever mechanism or (any desired) linear motor, for example in the form of a plunger-type armature (“solenoid”) which is movably guided in an electrically loaded coil.

In order to achieve smooth operation of the device according to the invention and in particular to ensure that in each case only one closing element is entrained by the ram and driven into the opening channel of the housing of a sample container, the device according to the invention can preferably comprise a separating apparatus. This can preferably comprise a feed channel in which the closing elements are arranged in succession and via which these are fed in succession to a transfer position located in the movement path of the ram. The movement of the closing elements in the feed channel can in this case take place as a result of the force of gravity. Alternatively or in addition, any other desired transport means, for example means for exerting vibrations or compressed-air transport means, can also be used.

The device according to the invention can furthermore have a barrier element which temporarily fixes the individual closing elements in the transfer position. The fixing of the respective closing element by the barrier element is preferably only released when the ram entrains it. This can be achieved in a simple manner by means of a spring-loaded or spring-mounted barrier element which is laterally displaced when the force exerted by the ram on the closing element is exceeded, such that the movement path of the closing element is released.

In a further preferred embodiment of the device according to the invention, the latter has supporting means for supporting the transport of the closing element from the storage container to the ejecting means. These may act preferably in a vibrating and/or pneumatic manner. The supporting means can effect transport in isolation or only support transport, for example exert transport in conjunction with transport as a result of the force of gravity.

Preferably, the ram may be integrated in an exchangeable manner in the device. Such a configuration is expedient in particular in the case of a use for closing sample containers for a biotechnological method, for example a PCR process, since particular requirements are placed on sterility there. The exchangeable integration of the ram into the device thus allows simple and cost-effective maintenance in order to meet the sterility requirements for such applications. Alternatively or in addition thereto, the ram may also be provided with an exchangeable (surface) cover. This embodiment can make it possible to meet the requirement of sterility of the system with—compared with an exchangeable ram—lower costs.

Preferably, the device has at least one sensor for sensing the ejection of a closing element, the filling level of the storage container and/or the force exerted by the ram on the respective closing element. Such a sensor makes it possible to monitor and document the closing process.

In a preferred embodiment of the system according to the invention, the contact area of the ram which comes into contact with the closing element during ejection may be configured in a larger manner than the external cross-sectional area of the opening channel of the housing of the sample container. As a result, the portion of the housing that surrounds the opening channel can serve as a (maximum) stop for the ram, as a result of which it is possible to prevent the closing element from being driven further than intended into the opening channel of the housing. In addition, the relatively large area of the ram can ensure that reliable closing can be achieved even in the case of relatively imprecise positioning of the device relative to the housing of the sample container. This embodiment should preferably be combined with means for limiting the forces exerted by the ejecting means on the closing element, in order to avoid damage to the sample container.

The system according to the invention can furthermore have a sensor which can determine the position of the closing element in the housing of the sample container. This too may be expedient or necessary to check and document the closing process.

One possibility for this purpose may be to form the housing of the sample container in an optically transparent manner at least in one portion of the closing portion, with the sensor comprising means for detecting the refractive index of the housing material in the transparent portion. The operation of the sensor can accordingly be based on determining a change to the refractive index, this change being caused by the fact that, during the transition of the light from a first solid (wall of the opening channel at the location at which the closing element is positioned) to a second solid (closing element), there is no total reflection at the inner wall of the opening channel, whereas, in the event of a transition from a solid (wall of the opening channel) to air (or another gas), there is partial reflection at the inner wall.

Preferably the housing may form a shoulder for forming a bearing surface. The forces that are to be applied to introduce the closing element (typically from 60 N to 130 N, at most 250 N) can be supported at a holder supporting the sample container via said bearing surface. In particular, the bearing surface can be formed at a point of the housing that is located in the vicinity of the closing portion of the opening channel. It is thus possible to prevent the forces from being transmitted via other portions of the housing, which may be formed with thinner wall thicknesses and may therefore be more sensitive (in particular the wall of the housing surrounding the sample space).

A storage container for use in a device according to the invention has a housing and a guiding and/or bearing apparatus arranged within the housing, a plurality of spherical closing elements being arranged alongside one another in a row therein.

Preferably, the guiding and bearing apparatus can have a guiding and bearing channel that extends in a spiral shape.

Further preferably, the housing of the storage container may have a filling opening which is closed non-releasably with the closing elements after the storage container has been filled. Accordingly, such a storage container is preferably provided according to the invention as a single use product, which can be advantageous in particular for sterility reasons. From this point of view, it is also possible for the ejecting means (in particular the ram) to be integrated in the storage container provided as a single use product.

The invention will be explained in greater detail hereinafter on the basis of exemplary embodiments illustrated in the drawings.

In the drawings:

FIG. 1: shows a sample container of a system according to the invention;

FIG. 2: shows a detail of the sample container of FIG. 1 in a sectional side view;

FIG. 3: shows a further detail of the sample container of FIG. 1 in a sectional side view;

FIG. 4: shows the introduction of the closing element into the sample container according to FIGS. 1 to 3 by means of a ram in a first embodiment;

FIGS. 5 and 6: show the introduction of a closing element into a sample container according to FIG. 1 by means of a ram in a second embodiment;

FIG. 7 a: shows the force curve when introducing closing elements into sample containers according to FIGS. 1 to 3 with use of a ram according to FIG. 4;

FIG. 7 b: shows the force curve when introducing closing elements into sample containers according to FIGS. 1 to 3 with use of a ram according to FIGS. 5 and 6;

FIGS. 8 a and 8 b: show a sample container of a system according to the invention in a second embodiment in two different sectional illustrations;

FIGS. 9 a and 9 b: show a sample container of a system according to the invention in a third embodiment;

FIG. 10: shows a sample container of a system according to the invention in a fourth embodiment;

FIG. 11: shows a storage container of a device according to the invention for automatically closing sample containers in a first embodiment;

FIG. 12: shows a closing unit of a device for the automated closing of sample containers according to the invention;

FIG. 13: shows a basic illustration of the operating principle of the closing unit according to FIG. 12;

FIG. 14: shows an isometric view of a storage container of a device according to the invention for automatically closing sample containers in a second embodiment;

FIG. 15: shows the storage container according to FIG. 14 in combination with a closing unit in a longitudinal section;

FIG. 16: shows the storage container according to FIG. 14 in combination with an alternative closing unit in a longitudinal section;

FIG. 17: shows the integration of the components according to FIGS. 11 and 12 in an automated closing device;

FIG. 18: shows the integration of the automated closing device according to FIG. 17 in a device for carrying out a PCR;

FIG. 18: shows a schematic illustration of an alternative supply of closing elements to a device for the automated closing of sample containers according to the invention; and

FIGS. 20 a to 20 f: show comparisons of a “normal” force curve to deviating force curves, produced by various causes.

FIG. 1 shows a sample container 1 according to the invention in a first embodiment. The sample container 1 comprises a housing 2, which is formed in a first portion (head portion 3) and a second portion (middle portion 4) with a largely cylindrical lateral surface. The lateral surface has just a small conical tapering, which is used in order to more easily demold the housing 2 consisting of plastic after injection molding. The end of the middle portion 4 opposite the head portion 3 is adjoined by an end portion 5, in which the housing 2 tapers and is therefore formed in a tapering manner in the broader sense. In the end portion 5, the housing 2 is formed from an (optically) transparent material, which enables the use of optical measuring elements within the scope of a biotechnological method, such as a PCR process, in which the sample container 1 is to be used.

On the outer face between the head portion 3 and the middle portion 4, the housing 2 forms a shoulder 6, which is used as a bearing surface, via which the housing 2 is supported on a sample container support 7 (see FIG. 2).

Within the middle portion 4 and the end portion 5 of the housing 2, a sample space is formed, wherein the wall thickness of the housing 2 in these two portions is largely constant, such that a sample space portion which is again largely cylindrical is formed within the middle portion 4, and a conically tapering sample space portion formed with a rounded tip is formed in the end portion 5 of the housing 2.

In the head portion 3 of the housing 2, an opening channel is formed, which makes it possible to fill the sample container 1 with the sample to be examined. After filling, the sample space is closed by the introduction of a spherical closing element 8 in the manner according to the invention. The closing effect, that is to say both the sealing and the fixing of the closing element 8 in the opening channel, is achieved in that the largest outer diameter of the closing element 8 is slightly larger than the opening channel in a defined portion (closing portion 11) (see FIG. 2) and the closing element 8 is therefore fixed in a wedged manner in the opening channel.

Starting from the upper (free) end of the head portion 3, the opening channel is first provided with an entry chamfer 9, which defines a relatively (based on the outer diameter of the closing element 8) large opening cross section (largest diameter: 4.5 mm). The entry chamfer 9 facilitates the central positioning of the closing element 8 (largest diameter 4.1 mm to 4.2 mm). The entry chamfer 9 transitions into a first annular protrusion 10, which reduces the opening cross section (diameter: 3.7 mm) of the opening channel compared to the opening cross section in the closing portion of the opening channel (diameter: approximately 4.0 mm). In order to introduce the closing element 8 into the opening channel, it is loaded by a force (component) which is directed coaxially with or parallel to the longitudinal axis of the housing 2, specifically in the direction of the end portion of the housing 2.

The force is so great that it leads to a deformation both of the housing 2 in the region of the head portion 3 and of the closing element 8 itself, which makes it possible for the closing element 8 to pass the first protrusion 10 and to be inserted as far as the closing portion 11 of the opening channel. There, the closing element 8 is fixed in a force-locked manner, that is to say wedged, by means of its larger (maximum) diameter compared to the diameter of the opening channel in the closing portion 11. Here, the forces are achieved by a (largely elastic) deformation of the housing 2 in the region of the closing portion 11 and also of the closing element 8. Due to the symmetrical force-locked fixing of the spherical closing element 8 in the region of its largest cross section, the reaction forces that act from the wall of the opening channel onto the ball (and vice versa) do not have any component in the longitudinal axial direction of the housing. Once introduced into the closing portion 11, the closing element 8 is thus securely held, provided no significant external forces act thereon in the longitudinal direction of the housing 2.

The first protrusion 10, which has to be passed by the closing element 8 when introduced into the closing portion 11, is used on the one hand as an end stop that prevents the closing element 8 from being slid out from the opening channel in the event of the creation of an overpressure within the closed sample space, for example caused by heating within the scope of a biotechnological method, such as a PCR process, and thus prevents the sample container 1 from being opened undesirably.

Furthermore, this protrusion 10 is used to produce a force curve which is characteristic as the closing element 8 is introduced and on the basis of which an actual introduction of the closing element 8 as far as the closing portion 11 can be detected (in the manner of a locking into place).

The transition of the opening channel into the sample space of the housing 2 is formed as an annular shoulder. This shoulder constitutes a second protrusion 12, which is used as an end stop for the closing element 8 and therefore delimits the closing portion 11 of the opening channel on the side of the sample space.

The length of the closing portion 11 of the opening channel is dimensioned such that the closing element 8 can be displaced therein over a specific distance x before it contacts one of the two protrusions 11, 12 (see FIG. 3). This distance is limited in the present case to 0.7 mm at most, since experience has demonstrated that, with a displacement of this type of the closing element 8, the process parameters (in particular pressure, temperature) within the sample space only change to such a small extent that no significant (negative) effects on the biotechnological method, such as the PCR process, are to be feared. This positional tolerance of the closing element 8 within the closing portion 11 also has the advantage that relatively large tolerances in the production of the housing 2 and of the closing element 8 can be specified, whereby the corresponding tools can be subject to less stringent requirements.

FIGS. 4 to 6 show the use of a ram 13 (in two embodiments) in order to slide the closing element 8 into the opening channel. In the embodiment according to FIG. 4, the ram 13 has an outer diameter of 3.6 mm (or smaller), which is therefore smaller than the inner diameter of the opening channel in the region of the first protrusion 11. The ram 13 can therefore dip into the opening channel. To this end, the movement of the ram should be controllable in a precise manner in order to prevent said ram from pressing the closing element 8 with force against the second protrusion serving as an end stop, which could lead to damage of the housing 2 or of the closing element 8. In the embodiment of a ram 13 according to FIGS. 5 and 6, the outer diameter of the ram 3 is therefore considerably larger than the inner diameter of the opening channel in the region of the entry chamfer 9. The movement of the ram 13 is therefore delimited at the latest by the fact that it contacts the free end of the housing 2. A pressing of the closing element 8 by means of the ram against the second protrusion 12 serving as an end stop can therefore be easily avoided. A further advantage of the large contact area of the ram 13 is that the closing element 8 can be pressed in steadily without difficulty, even if the ram 13 is not arranged exactly centrally above the closing element 8 (see FIG. 6).

FIG. 7 a shows an exemplary force curve (force F over the ram path I) for a closing process with use of a ram according to FIG. 4. In a first portion (a) of the force curve, the force is practically zero; this portion defines the displacement of the ram 13 until it contacts the closing element 8. This is followed in a second portion by a sharp rise of the force as far as a first maximum value (b) (first extreme point of the curves), which is necessary in order to allow the closing element to pass the first protrusion 10. This force then falls as far as a second extreme point (c), which defines the force (which is then only slightly rising due to the slightly conical design of the opening channel, see portion (d)) which is necessary to displace the ball in the closing portion 11. This force corresponds substantially to the force that is produced from the friction between the wall of the opening channel in the closing portion 11 and the contacting portion of the closing element 8. If a closing process is carried out correctly, the exertion of force ends anywhere in portion (d) of FIG. 7.

If the ram 13 dips too deeply into the opening channel however, the closing element may be pressed thereby against the second protrusion 12, which is again evidenced by a sharp rise in force (portion (e)). This rise may be limited (that is to say in accordance with the depth of dip of the ram 13) by the breaking load of the sample container 1 (and, where appropriate, also of the closing element 8 or of the ram 13) ((f)), whereby the force falls to a considerably lower level (portion (g)).

FIG. 7 b shows a corresponding exemplary force curve for the use of a ram according to FIGS. 5 and 6. The force curve in portions (a) and (d) as well as therebetween corresponds to that in FIG. 7 a. After portion (d), there is then a rise in force (h), which is sharper than that with the curve according to FIG. 7 a. This is produced as a result of the contact between the ram 13 and the edge of the sample container 1. The ram 13 should then only be moved further over a relatively short path in order to avoid overloading the sample container 1 (or the ram 13). To control the stroke of the ram, the force curve can be evaluated such that, for example once the end of the portion (h) has been reached, a (force) limit value is reached, which for example may lead to a deactivation of a ram drive. In FIG. 7 b, the further force curve that leads to a rupture of the sample container due to overload is also illustrated with a dashed line arrangement. This is characterized by a continuation of portion (h) (portion (i)), at the end of which the rupture occurs. This is characterized by a direct fall in force to a level close to zero (portion (k)).

FIGS. 20 a to 20 f show exemplary deviations from the “normal” force curves described previously. It is possible to determine the appropriate fault source from these deviations. Here, the deviating force curve is illustrated by a continuous line, whereas the “normal” force curve is shown in a dashed manner. FIG. 20 a shows two deviating force curves, wherein the dimensioning or the material properties of the sample container in the region of the opening channel and/or of the closing element are not correct. FIG. 20 b shows two deviating force curves, wherein the vertical alignment of the closing element, that is to say the distance between the closing element and the ram, is too little or too large. In the case of the deviating force curve according to FIG. 20 c, the horizontal alignment is not correct, that is to say there is insufficient conformity between the longitudinal axes of the sample container and of the ram. This may lead to an impairment of the movement of the closing element. FIG. 20 d shows a deviating force curve which is produced if there is a fault concerning the closing element and the ram moves without substantial application of force until colliding with the sample container. The deviating force curve illustrated in FIG. 20 e can be produced if the contact surfaces of the closing element and/or of the sample container do not correspond to the requirements. By contrast, FIG. 20 f shows a deviating force curve which can be produced in the event of the rupture of a sample container.

FIGS. 8 a and 8 b show a second embodiment of a sample container 1, wherein two closing elements 8 are fixed in a force-locked manner in a common closing portion 11 of the housing 2. A second sample space is thus formed between the two closing elements 8. The corresponding embodiment of the opening channel, by contrast with the illustration in FIG. 8, can be selected arbitrarily in accordance with the exemplary embodiment according to FIGS. 1 to 3, that is to say in particular can be provided with one or more protrusions. Furthermore, a bypass channel 14 is formed in the wall of the housing between the lower sample space and the closing portion 11 and also between the closing portion 11 and the upper, open end of the sample container 1. The upper bypass channel 14 is used to balance an overpressure in the two sample spaces, which would otherwise be produced as a result of the relatively deep introduction of the closing elements. By contrast, the lower bypass channel 14 is provided, for example within the scope of the PCR process, to transfer a sample contained in the upper sample chamber into the lower sample chamber, as is illustrated in FIG. 8 a. To this end, the lower closing element 8 is slid by means of the upper closing element 8 into the portion of the opening channel/sample space comprising the lower bypass channel 14, such that the sample can flow from the upper sample chamber via the lower bypass channel 14, past the lower closing element 8, and into the lower sample chamber.

FIGS. 9 a to 9 b show a sample container 1 in a further embodiment, in which said sample container is to be opened again by pressing the closing element 8 by means of a ram 13 completely into the sample space as far as the closed end. The sample liquid displaced during this process can flow off via a bypass channel 14 formed on one side in the wall of the housing 2 and can thus be removed from the sample container 1.

FIG. 10 shows a sample container 1, wherein the housing 2 is provided in the region of the sample space with a varying wall thickness. In the region of the sample space which receives the sample, the housing 2 has a minimal wall thickness, for example from 0.2 to 0.3 mm. A thin wall thickness simplifies the examination of the sample by means of optical methods. In a portion of the sample space which forms a dead space (that is to say with no sample contained therein), the wall thickness is thicker, by contrast (for example twice as thick, for example 0.4 to 0.6 mm), whereby not only can the mechanical stability of the housing 2 be increased, but in particular also an evaporation of the sample through the housing 2 can be reduced.

FIGS. 11 and 12 show individual components of an automated closing device (see FIG. 17) which is to be used in a device for carrying out a PCR process (see FIG. 18).

Here, FIG. 11 shows a storage container 15, in which a drawn-out guide 16 running in a spiraled manner is arranged and is used to receive and guide a multiplicity of closing elements 13 of a sample container 1. The lower end of the guide 16 ends in an outlet opening, via which the closing element can be transferred to a closing unit 17, as is illustrated in part in FIG. 12. The storage container 15, which can be sold as a filled disposable container, can be fastened for this purpose to the front end of the closing unit 17.

The closing unit 17 comprises an electric motor arranged in a housing 18, said electric motor being able to drive a drive disc 19 in rotation. The drive disc 19 is provided decentrally with a bolt 20, which is guided in a slot 21 of a ram guide 22. The guidance of the bolt 20 in the slot 21 translates the rotational movement of the drive disc 19 into a cyclical upward and downward movement of the ram guide 22, inclusive of a ram 13 fastened thereto, as is illustrated in principle in FIG. 13. With each downward movement of the ram 13, a closing element 8 held in a transfer position is entrained and is pressed via a discharge opening of the closing unit into the opening channel of a housing 2 of a sample container 1 arranged therebelow (not illustrated in FIG. 13). Once the ram 13 has been raised again, a further one of the closing elements 8 stored temporarily in succession in a feed channel 23 can then roll (as a result of the force of gravity) into the transfer position, where it is held via a spring-mounted barrier element 24. With the subsequent downward movement of the ram 13, the next closing element 8 is then entrained, wherein the barrier element 24 is displaced to the side in order to release the discharge opening.

Alternatively, it is also possible for the movement back and forth of the ram 13 to be caused not by a unidirectional rotation (through 360°) of the drive disc 19, but for said drive disc to also be drivable by means of a stepper motor having a (cyclical) rotational direction change in order to move the ram 13. Any, and in particular even changing, displacement paths, speed profiles, etc. of the ram 13 can thus be implemented. This can be used in particular to limit the force exerted by the ram 13 onto the closing element 8 (in conjunction with a measurement process using sensors) by means of a corresponding control of the stepper motor. This embodiment can also be developed such that the cyclical movement of the ram 13 is produced in principle by a continuous rotation of the drive disc 19, and the drive motor only stops the movement and reverses its direction of movement if there is a risk that the permissible force will be exceeded.

FIG. 14 shows a storage container 15 a for a multiplicity of closing elements 8 in an alternative embodiment. The main differences from the storage container 15 according to FIG. 11 lie in the fact that on the one hand the closing elements 8 are stored in an unsorted manner, that is to say as a packing, in a storage space of the storage container 15 a and on the other hand a ram 13 a for dispensing the closing elements 8 individually from the storage container 15 a is integrated. The base and wall surfaces of the storage container 15 a are formed such that the closing elements arranged at the bottom in the packing are fed to a dispensing channel 29, of which the inner diameter is only slightly larger than the outer diameter of the closing elements. It is thus ensured that the closing elements reach a transfer position individually, where they can be caught and entrained by the ram 13 a.

FIG. 15 shows the use of the storage container according to FIG. 14 in combination with an alternative closing unit 17 a (only illustrated in part). A particular feature of this combination is for use of a total of two rams, on the one hand the ram 13 a integrated into the storage container 15 a for dispensing the closing elements 8 individually from the storage container, whereby the closing elements are placed on a sample container 1 arranged beneath. By contrast, a second ram 13 integrated into the closing unit 17 a is used to drive the closing element 8 placed beforehand on a (different) sample container 1 into the closing portion of the opening channel of this sample container. The main advantage of the use of two rams lies in improved hygiene when the storage container 17 a, inclusive of the ram 13 a, is to be used as a disposable container, which is therefore disposed of after use.

As can be seen from FIG. 15, the movements of the two rams 13, 13 a are coupled to one another. To this end, a bolt 30, which is spring-mounted in a portion of the ram 13, engages in a corresponding opening in the ram 13 a. The movement of the ram 13 is thus transmitted to the ram 13 a. The ram 13 itself is constructed in a number of parts and comprises a ram element 31, which is mounted in an axially displaceable manner in the lower end of a main body 32 of the ram 13. The ram element 31 is connected via a central bore with an inner thread to a threaded pin 33, which is part of a force limitation unit. The force limitation unit additionally comprises a spring 34 (cylindrical helical spring), which is biased by two contact plates 35. The bias forces are supported here via an abutment of the upper contact plate 35 and an annular protrusion of the ram element 31 against corresponding contact areas of the main body 32. The bias of the helical spring can be changed via the depth to which the threaded bolt 33 is screwed into the ram element 31, and a limit value for the force exerted by the ram element 31 onto the closing element 8 can thus be adjusted. As soon as this force is exceeded, the ram stroke is compensated for (partially) by a retreat of the ram element 13.

FIG. 16 shows a closing unit 17 b, which corresponds substantially to that of FIG. 15 in terms of function, but is of simpler construction however. A (mechanical) force limitation unit is not provided here, rather this is achieved electronically by a corresponding controller of the ram drive. The ram element 31 a is therefore integrated in the main body 32 a of the ram 13 in an axially stationary manner, and the bolt 30 a for entrainment of the ram 13 a of the storage container also is not spring-mounted. In this case, the storage container 15 a corresponds to that of FIG. 15.

The closing units 17, 17 a, 17 b and storage containers 15, 15 a can be integrated into an automatic closing device 25, as is illustrated in FIG. 17. There, the unit formed from a closing unit 17 and storage container 15 can be displaced by a linear drive 26 along a first axis (in the transverse direction).

The automatic closing device according to FIG. 17 can in turn be integrated into a device for carrying out a PCR process according to FIG. 18, in such a way that the closing device 25 as a whole is displaceable by a second linear drive 27 along a second axis (in the longitudinal direction), which is oriented perpendicularly to the first axis (the axis of displacement of the linear drive 26 of the closing device). The displaceability of the unit formed of the closing unit 17 and storage container 15 in two axes oriented perpendicularly to one another makes it possible to remove a multiplicity of housings 2 of sample containers 1, which are positioned in a number of rows in a total of three sample container supports 7, and to close each of said housings with a closing element 8. The correct placement of the closing element 8 in the individual housings 2 is checked here with the aid of a laser distance sensor (not illustrated).

FIG. 19, in a schematic illustration, shows the possibility of fixing the closing elements 8 releasably in a conveyor belt (blister tape) 28 and of positioning said closing elements successively over a movement of the conveyor belt 28 in the transfer position, from which they can then be introduced by means of a ram 13 into the opening channel of a sample container 1. The conveyor belt 28 has a main belt 36 provided with openings arranged at regular intervals, wherein, in the region of each of the openings, a closing element 8 rests on one side of the main belt 26 and is surrounded there by a retaining belt 37 and is thus held in place. The individual closing elements can be removed from the conveyor belt 28 through the prospective opening and driven into the opening channel of the sample container 1 by means of the ram 13. 

1. A device for closing a sample container with a spherical closing element, comprising a storage container for a plurality of spherical closing elements, ejecting means for ejecting one of the closing elements through a discharge opening in a housing of the device, and means for limiting the forces exerted by the ejecting means on the closing element.
 2. The device as claimed in claim 1, wherein said ejecting means comprises a ram.
 3. The device as claimed in claim 2, comprising drive means for periodic movement of the ram.
 4. The device as claimed in claim 3, comprising a rotary drive which is connected to the ram via a gear mechanism.
 5. The device as claimed in claim 1, comprising a separating apparatus for individually positioning the closing elements in a transfer position in a movement path of the ram.
 6. The device as claimed in claim 5, wherein said separating apparatus comprises a feed channel, via which the closing elements are transported into a transfer position.
 7. The device as claimed in claim 6, comprising a barrier element for temporarily fixing individual closing elements in a transfer position.
 8. The device as claimed in claim 1, comprising a means, which acts preferably optionally in a vibrating and/or pneumatic manner, for transporting or for supporting transport of the closing elements from the storage container to the ejecting means.
 9. The device as claimed in claim 1, wherein said ejecting means are integrated in an exchangeable manner.
 10. The device as claimed in claim 1, wherein said ejecting means are provided with an exchangeable cover.
 11. The device as claimed in claim 1, comprising at least one sensor for sensing ejection of a closing element, filling level of the storage container and/or forces exerted by the ejecting means on the closing elements.
 12. A system comprising: a device as claimed in claim 1, and; a housing of a sample container, wherein the housing forms a sample space for receiving a sample and has at least one circular opening, wherein the opening extends in a channel-like manner into the sample space, and wherein the diameter of the closing elements only exceeds the diameter of the opening channel in at least one closing portion to such an extent that one of the closing elements can be fixed in a force-locked manner by a largest circumference thereof in the closing portion.
 13. The system as claimed in claim 12, wherein a contact area of the ejecting means that comes into contact with the closing elements is larger than an external cross-sectional area of an opening channel of the sample container.
 14. The system as claimed in claim 12, comprising a sensor for detecting presence and/or position of the closing element in the housing of the sample container.
 15. The system as claimed in claim 14, wherein said housing of the sample container is formed in an optically transparent manner at least in one portion of the closing portion, and the sensor comprises means for detecting the refractive index of housing material in a transparent portion.
 16. A storage container having a multiplicity of spherical closing elements capable of being used in a device as claimed in claim 1, said container comprising a housing and a guiding and/or bearing apparatus which is arranged within the housing and in which the closing elements are arranged alongside one another in a row.
 17. The storage container as claimed in claim 16, wherein said guiding and bearing apparatus has a guiding and bearing channel which extends in a spiral shape.
 18. The storage container as claimed in claim 16, wherein said housing has a filling opening which can be closed non-releasably with the closing elements after the storage container has been filled.
 19. The storage container as claimed in claim 16, comprising an integrated ejecting means for ejecting one of the closing elements through a discharge opening in the housing. 